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TP53 aberrations are found in approximately 10% of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and are considered early driver events affecting leukemia stem cells. In this study, we compared features of a total of 84 patients with these disorders seen at a tertiary cancer center. Clinical and cytogenetic characteristics as well as immunophenotypes of immature blast cells were similar between AML and MDS patients. Median overall survival (OS) was 226 days (95% confidence interval [CI], 131-300) for the entire cohort with an estimated 3-year OS rate of 11% (95% CI, 6-22). OS showed a significant difference between MDS (median, 345 days; 95% CI, 235-590) and AML patients (median, 91 days; 95% CI, 64-226) which is likely due to a different co-mutational pattern as revealed by next-generation sequencing. Transformation of TP53 aberrant MDS occurred in 60.5% of cases and substantially reduced their survival probability. Cox regression analysis revealed treatment class and TP53 variant allele frequency as prognostically relevant parameters but not the TP53-specific prognostic scores EAp53 and RFS. These data emphasize similarities between TP53 aberrant AML and MDS and support previous notions that they should be classified and treated as a distinct disorder., (© 2022. The Author(s).)

A number of risk factors for the occurrence of neutropaenic fever after haematopoietic stem cell transplantation (HSCT) have been proposed. We were interested in whether these factors remain valid for several early infection-related outcomes when applied to a homogeneous group of patients in uni- and multivariate analyses. Therefore, we analysed 144 consecutive patients with lymphoproliferative disorders receiving autologous peripheral blood HSCT. Variables tested as potential risk factors for the occurrence of fever, documented infection (DI), microbiologically documented infection (MDI) or failure of first-line antimicrobial therapy were sex, conditioning regimen, prolonged neutropaenia, low number of CD34+ cells transplanted, purging, lack of selective gut decontamination, higher age and increased body mass index. In uni- and multivariate analyses, conditioning including total body irradiation was the only risk factor for the occurrence of fever, and neutropaenia >or=10 days was the only factor associated with failure of first-line antimicrobial therapy. None of the variables tested was associated with an increased risk for DI or MDI. This analysis suggests that a number of previously proposed risk factors actually are of minor clinical relevance for early infections in the majority of patients receiving autologous HSCT.

We retrospectively evaluated 107 fiberoptic bronchoscopies with and without transbronchial lung biopsy (TBLB) in 98 consecutive patients with haematologic malignancies and pulmonary infiltrates. Bronchoalveolar lavage (BAL) was performed in 45 and BAL plus TBLB in 62 procedures. There was no procedure-related severe haemorrhage, pneumothorax or death. Infectious aetiology was identified in 26 of 107 (24%), toxic pneumonitis in 17 of 107 (16%) and neoplastic infiltration in 9 of 107 (8.5%) episodes. Combined BAL and TBLB was significantly superior to BAL alone with respect to the diagnosis of neoplastic infiltrates (p=0.008) and toxic pneumonitis (p<0.001) and should therefore be included in the diagnostic work-up of this patient cohort.

Acute myeloid leukemia (AML) associated with central diabetes insipidus (DI) and chromosomal aberrations is characterised by a very poor prognosis. We present a 28-year-old female with AML FAB M0, preceding DI and cytogenetic abnormalities (monosomy 7 and inversion of chromosome 9). Complete remission was achieved with FLAG after she was refractory to two different induction regimens. Prolonged neutropenia resulted in invasive pulmonary aspergillosis. Allogeneic stem cell transplantation from a matched unrelated donor was performed using a reduced-intensity conditioning regimen. Desmopressin substitution for DI was withdrawn after transplant without recurrence of symptoms. Initial antifungal treatment, including liposomal amphotericin B, caspofungin and itraconazole, was replaced by voriconazole after deterioration of pulmonary aspergillosis, resulting in improvement, stabilisation and finally, also as the combined effect of discontinuation of the immunosuppressive therapy, in disappearance of signs and symptoms. Thirteen months after transplant, the patient is in continuous complete remission. The presented case study thus demonstrates that high-risk AML with concomitant invasive fungal infection may be safely and effectively treated by nonmyeloablative stem cell transplantation and long-term administration of voriconazole.

Therapy-related leukemia cutis has not yet been described. We report a 55-year-old male who developed aleukemic leukemia cutis 15 months after chemotherapy and radiotherapy for non-Hodgkin's lymphoma. Despite intensive therapy including allogeneic hematopoietic stem cell transplantation, the patient died of progressive disease. Sequence analysis of the TP53 gene and screening for defective DNA mismatch repair revealed no abnormalities. This case demonstrates that therapy-related aleukemic leukemia cutis is an aggressive disorder resistant to conventional antineoplastic treatment approaches. As the number of patients developing therapy-related myelodysplasia or leukemia is increasing, clinicians might be confronted more frequently with atypical, extramedullary presentations of these disorders.

The study was performed to describe the time course of serum cardiac troponin T (cTnT) elevations for the early detection of anthracycline cardiotoxicity. cTnT was analyzed serially in 78 patients with hematological malignancies receiving 142 treatment cycles including various anthracyclines. cTnT positivity was defined as an increase in cTnT >or=0.03 ng/ml and was observed in 12 patients (15%) during 16 treatment cycles (11%). Peak cTnT levels were observed on day +21.5 (median, range: day +6 to day +35) after initiation of anthracycline therapy. cTnT positivity lasted >or=3 days in 63% of cycles and began to occur after a median of two anthracycline doses. Follow-up echocardiography in 28 patients showed a greater decrease in left ventricular ejection fraction (LVEF) in cTnT-positive patients compared to the cTnT-negative group (10% vs 2%, p=0.017). Age, gender, and pretreatment LVEF had no influence on the occurrence of cTnT positivity. Serial measurement of serum cTnT reveals delayed subclinical myocardial damage even after minor anthracycline exposure, may identify patients at risk for subsequent myocardial dysfunction, and suggests prolonged damage to the cardiac myofibrillar system.

It is yet undetermined whether patients with different hematological malignancies have different propensities to infectious complications after high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 136 cycles of HDC and autologous HSCT in 114 patients with acute myeloid leukemia (AML, 24 cycles), non-Hodgkin's lymphoma/Hodgkin's disease (NHL/HD, 55 cycles), and multiple myeloma (MM, 57 cycles) with respect to early infectious complications. Median duration of neutropenia was longer in patients with AML and NHL/HD than in patients with MM (11 days vs 8 days) and after conditioning including total body irradiation (TBI) compared with chemotherapy only preparative regimens (11 days vs 7 days). Fever requiring antimicrobial therapy was observed in 88 percent of cycles, with fever of unknown origin (FUO) accounting for 60 percent of febrile episodes. There was no proven fungal infection, but one case of probable invasive pulmonary aspergillosis. Microbiologically documented infections were seen in 29 percent and clinically documented infections in 11 percent. Response to first-line empirical antibiotic therapy was better for FUO than for documented infections (70 percent vs 40 percent). Patients with TBI as part of their conditioning regimen had more overall infections than patients without TBI (96 percent vs 82 percent). There were no differences with respect to the type or incidence of infections between patients with AML, NHL/HD, and MM. Patients with different hematological malignancies have similar rates of early infectious complications after HDC and autologous HSCT. TBI may be associated with an increased risk for infections in the early post-transplant period.

Monoclonal antibodies recognizing hematopoietic antigens are increasingly being used to target therapy directly at leukemic cells, with the aim of achieving sustained remission with little systemic toxicity. Administration of anti-CD33 calicheamicin immunoconjugate is commonly regarded as being safe, with only moderate systemic non-hematological side effects. We report on two cases of hepatic veno-occlusive disease in heavily pretreated patients presenting with relapsed acute myeloid leukemia (AML). Since significant liver toxicity prevented further specific therapy in both patients, we recommend that antibody therapy with anti-CD33 immunoconjugate should be applied with caution in patients presenting with risk factors for the development of hepatic veno-occlusive disease.

Due to their homing properties, extranodal marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) type remain localized for long periods of time, and therefore have an excellent prognosis. However, if generalization and/or transformation into a diffuse large-cell lymphoma occurs, the prognosis deteriorates and no established treatment concepts are yet available. We report about a 57-year-old female patient with relapsed transformed stage-IV extranodal MZBL of MALT type of the entire gastrointestinal tract who was successfully treated using salvage chemotherapy followed by BEAM conditioning [BCNU 1,3-bis-2-(chloroethyl-1-nitrosourea), etoposide, cytosine arabinoside, and melphalan] and autologous peripheral stem cell transplantation. Follow-up revealed a sustained complete remission for 22 months.

Acute myelofibrosis is a rare, malignant hematological disorder of unknown etiology with an inevitably fatal outcome. Here we present the study of a 63-year-old Caucasian man with acute onset of pancytopenia. Repeated bone marrow biopsies showed dense fibrosis and hypoplastic hematopoiesis raising various differential diagnoses of malignant and nonmalignant conditions. Bone marrow scintigraphy and magnetic resonance imaging (MRI) showed areas suggesting neoplastic infiltration, mainly in both femurs and tibias. Histological examination of a surgical biopsy of the left tibia revealed acute megakaryoblastic leukemia. As the patient refused polychemotherapy, therapy with interferon gamma was initiated but discontinued prematurely because of intolerable side effects. The presented case therefore suggests that the combination of bone marrow scintigraphy and MRI is a valuable diagnostic tool in patients presenting with myelofibrosis of unknown origin.

The study aimed to increase the sensitivity of somatostatin receptor (SR) specific scintigraphy for the detection of non-Hodgkin's lymphoma (NHL). Ten selected patients presenting with histologically proven NHL and with 50% to 100% bone marrow involvement were injected with 20 micrograms octreotide labeled with a mean of 254 MBq 111In. The results were recorded with a double head gamma camera by long-time SPET (60 sec per frame, 3 interval) of neck/thorax and abdomen/pelvis. To show bone marrow displacement by lymphoma cells, SPET of the same regions (15 sec per frame, 3 interval) was recorded 3 to 7 days later after i.v. administration of 0.5-1 mg monoclonal anti-granulocyte antibody (Mab 250/183) labeled with a mean of 454 MBq 99mTc. This modality showed a person related sensitivity of 70%, a lesion related sensitivity of 48% (29/60), 60% (22/37) above and 30% (7/23) below the diaphragm. The sensitivity in detecting bone marrow involvement was 10%. Only 80% bone marrow infiltration with lymphoma cells in nodular configuration was shown by In-111-octreotide scintigraphy correlating with cold lesions in the anti-granulocyte scan. There was no false positive result; the smallest lesion correctly identified by SR scintigraphy had with a diameter of 1 cm, the largest lesion missed measured 3.5 cm. In conclusion, doubling the doses of octreotide and radiolabel and extended SPET recording improved to some extent the patient related sensitivity and visualized nodular bone marrow involvement in 10% of patients. The lesion related sensitivity improved mainly above but not below the diaphragm.

In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN) alpha-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2-90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n = 19) and untreated (n = 58) patients were 51 months (95% confidence interval [CI], 30-72) and 77 months (95% CI, 43-111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n = 6), PHR (n = 34), and less than PHR (n = 35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-alpha treatment identifies patients with a favorable long-term prognosis.

We present a 71-year-old patient with chronic lymphocytic leukemia diagnosed 27 years ago. Initially, the disease was staged as Rai II and the patient suffered from secondary immunoglobulin deficiency. Nevertheless, no treatment was necessary at that time. Because of disease progression a single course of chemotherapy was given in 1984. During the following year there was a constant decline of the WBC, accompanied by normalization of the immunoglobulins; both have remained stable ever since that time. However, there was still residual bone marrow infiltration, indicating persisting CLL. In 1993 cervical lymphadenopathy occurred with acute onset. A diagnostic lymphadenectomy revealed Hodgkin's disease of the nodular-sclerosing subtype. The patient was staged as II-III according to the Ann Arbor Classification and underwent radiation therapy. Cytogenetic examination of the bone marrow revealed a normal karyotype with an inversion of chromosome 9. This case demonstrates the rate coincidence of two lymphoproliferative disorders in the same patient. The clinical course and the immunologic findings of this patient are presented, together with a review of the literature.